The long-term objective of this research is to develop clinical tools which can be used to effectively evaluate new treatments for multiple sclerosis (MS). There are many new proposed treatments for MS which involve immunotherapy, oral tolerance, and alternative medicine techniques. These treatments need to be tested in animals and humans. Currently, there is a need for non-invasive techniques which can be used to differentiate acute and chronic brain damage as well as functional versus non-functional brain damage in MS patients. This project will be accomplished by sequentially and noninvasively evaluating anatomical, biochemical and functional properties of central nervous system tissue using 1) MR imaging, 2) echoplanar spectroscopic imaging (EPSI), which can be used to measure brain chemicals sensitive to neuronal and membrane damage, 3) electrophysiology, which can be used to measure nerve conduction amplitude and velocity, and 4) neurologic exams, which can be used to measure the Expanded Disability Stats Scale and Ambulatory Index. These exams will be performed on patients with remitting-relapsing MS, chronic progressive MS, MS patients receiving beta-interferon, and normal volunteers. With MS, lesions can occur in many places in the brain (i.e. brain stem, cerebrum, cerebellum) and it would be important to use multi-slice techniques for both MRI and spectroscopy in order to assess the progression of MS. Therefore, we are proposing to use EPSI to cover a large portion of the brain to measure metabolite changes in MS patients. In order to develop EPSI as an endpoint in testing new treatments for MS, we will correlate the electrophysiologic properties and clinical symptoms that accompany the biochemical changes measured by spectroscopy at several different times during a one year period. This correlation would be important in gaining a better understanding of the relationship between the nerve conduction and N-acetyl aspartate, a marker for neuronal damage.